This invention relates to a method and device for the controlled continuous administration of drug to the eye over a prolonged period of time. Still more particularly, this invention relates to an ocular drug device capable of bioeroding in the environment of the eye concurrently with the dispensing or at a point in time after the desired amount of drug has been administered.
Presently, diseases of the eye are still conventionally treated by periodically applying ophthalmic drugs in liquid or ointment form. While this method of administration is suitable in certain instances, a serious shortcoming is the failure of these types of dosage formulations to dispense the drug in a continuous manner. Periodic application of these dosage forms, even though they be applied at intervals during the day and night, results in the eye receiving a massive, but unpredictable, amount of drug at each time of application. The result of this intermittent administration is that the level of drug surges to a peak at the time the drug is applied to the eye, followed by a decline in concentration. Thus, a plot of drug in the eye and surrounding tissues vs time, after administration of several dosage forms a day has the appearance of a series of peaks which may surpass the toxic threshold of the drug and valleys which fall below the critical point needed to achieve the desired therapeutic effect. Further, drug administered via an ointment or liquid form of therapy is washed away rapidly by tear fluid, leaving the eye without medication until the next application. Moreover, in some ocular conditions characterized by constant deterioration, i.e. glaucoma, continuous treatment offers extremely important therapeutic advantages. Most ointment dosage forms presently available are in unsterilized form, and are generally difficult to use without impairment of vision.
It was proposed, late last century, to use water soluble drug containing gels of glycerinated gelatin that are shaped to the form of a lamella or eye disk. Such lamellae are applied to the eye to supply drug thereto. In use, the glycerinated gelatin vehicle dissolves almost instantly in tear liquid, producing the same type of effect as do liquid dosage forms. Thus, these disks are not suitable for providing for prolonged or sustained continuous release of a drug because of their rapid rate of dissolution. Further information on these water soluble dosage forms can be found in Remington's Pharmaceutical Sciences, XIII, pp. 547-8 (Mack Publishing Co., Easton, Pa., 1965); Fishburn, An Introduction to Pharmaceutical Formulation, p. 116 (Pergman Press Ltd., New York City, N.Y., 1965); and U.S. Pat. No. 273,410, Mar. 6, 1883.
Recognizing these disadvantages, a significant advance has recently been made in the field of ophthalmic drug delivery systems. In this regard, U.S. Pat. No. 3,416,530, granted Dec. 17, 1968, entitled "Eyeball Medication Dispensing Tablet", and Ser. No. 831,761, filed June 9, 1969, entitled "Ocular Insert", disclose a drug dispensing ocular insert which slowly releases drug to the eye for prolonged periods of time. Such ocular inserts are fabricated of materials that are biologically inert, non-allergenic, and insoluble in tear liquid. To initiate the therapeutic program, the ocular insert is placed in the upper or lower sac of the eye bounded by the surfaces of the sclera of the eyeball and conjunctiva of the lid. Since the material from which the ocular insert is formed is insoluble in tear liquid, it retains its integrity and remains intact during the course of therapy, acting as a reservoir to continuously release drug to the eye and surrounding tissues at a controlled rate. On termination of the therapeutic program the ocular insert is removed from the eye. Thus, a single such ocular insert provides the complete ophthalmic dosage regimen for a particular time period, on the order of 24 hours or longer. More frequent repeated applications which are necessary with liquids, ointments, or water soluble lamellae are avoided.
While the drug dispensing ocular inserts described above, which deliver drug to the eye continuously and in a controlled manner over a prolonged period of time, have proved to be markedly superior to the prior art ointments and liquids, there remain, however, improvements to be made. The ocular insert, after insertion in the eye sac, is designed to remain intact during the course of therapy, and does so since it is formed of material insoluble in tear liquid. On termination of the therapy program the insert must be removed, which may present difficulty and discomfort to some patients. In rare instances, the simple removal is made more difficult by unwanted migration of the insert to the upper fornix, where it may remain long after the entire drug supply has been released to the eye. Further, as is often conventional in ophthalmic practice, physician-patient contact is not of a sufficient degree so as to insure that medical instructions from the doctor are accurately carried out by the patient. Thus, in the case of the use of an insoluble ocular insert, there is no certainty that the patient will remove the device when scheduled to do so. This is particularly true with elderly patients who often forget or are simply unable to remove the device due to failing memory or eyesight.